Saturday, May 9, 2009

Travel-associated influenza A (H1N1) with a virus containing a mutation in PB2

Date: Fri 8 May 2009
From: Marcel Jonges

In the Netherlands, the 2nd laboratory confirmed human case of
influenza A (H1N1) virus infection was reported on 7 May 2009. A
53-year-old woman returned on the 30 Apr 2009 from Cancun, Mexico.
During the flight she developed an unproductive cough. Then, 2 days
later on 2 May 2009, she had a temperature of 38.6C and a sore throat
and consulted a general practitioner. Samples were submitted for
diagnostic evaluation and both the patient and her husband were
treated with oseltamivir. The patient recovered completely and
uneventfully, and samples collected 4 days later tested negative. The
virus was analyzed for presence of antiviral resistance markers in
the neuraminidase and for human adaptation markers in the PB2 protein
by direct sequencing.

The sequence data suggested that the virus was susceptible to both
oseltamivir and zanamivir. The amino acid 627 in PB2 (glutamicacid)
was not human-host-adapted, similar to recent swine influenza A
(H1N1) viruses. However, a glutamic acid to glycine amino acid
substitution was detected at position 677 in PB2. This mutation was
not observed in any of the A (H1N1) sequences submitted since 27 Apr
2009. Lam et al. (2008) postulated that this substitution could
reflect adaptation to mammalian hosts of highly pathogenic avian
influenza A (H5N1) viruses (1), as it was found to be under positive
selection based on phylogenetics of Indonesian viruses. Based on the
position of the mutation it might contribute to more efficient
human-to-human transmission by enhanced replicative efficiency of the
polymerase of the influenza A (H1N1) virus in humans [PB2 is a
polymerase component. - Mod.CP]. Experiments are underway to test the
relevance of this finding.

Reference:
----------
(1) Lam TT, Hon CC, Pybus OG, Kosakovsky Pond SL, Wong RT, Yip CW,
Zeng F, Leung FC, Evolutionary and transmission dynamics of
reassortant H5N1 influenza virus in Indonesia, PLoS Pathog. 2008 Aug
22;4(8):e1000130.
-snip-
hat-tip Science Teacher

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